Longevity Briefs: Repairing Our DNA With Bacterial Proteins

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Ageing isn’t just a single process – it has multiple components that will probably all need to be treated if we want to see a great leap forward for human health expectancy and life expectancy. Of all the underlying mechanisms of ageing, DNA damage might be the most challenging to overcome. DNA damage is caused by chemicals, radiation and replication errors, resulting in genetic mutations. Our cells randomly acquire genetic mutations throughout life that not only may eventually lead to cancer, but also disrupt the function of our tissues and organs.

Since every cell acquires mutations randomly, it’s difficult to imagine how even the most advanced and precise gene editing technology could fix this problem, since it would need to correct mutations specific to each individual cell. However, our cells are already extremely good at repairing their own DNA, and the cells of some other species are even better. We might be able to overcome DNA damage by significantly boosting the ability of our own cells to repair their DNA. In this study, researchers discover a bacterial protein that could potentially be transferred into other species to improve DNA repair.

The discovery:

In the study, researchers investigate Deinococcus radiodurans, a relatively common bacteria of interest due its ability to survive doses of radiation thousands of times higher than most other cells. The researchers knew that a protein called DNA Damage Repair Protein C (DdrC) was important for this ability, and set out to study its structure and work backwards to determine how it functions. DdrC appears to work by scanning the DNA molecule for breaks in one or both DNA strands, then isolates the breakage by either compacting the DNA or joining linear DNA strands to form circular strands. This prevents further damage to the DNA until other proteins can come to repair it, and enables the cell to stitch hundreds of DNA fragments back together again where a human cell would simply die.

While most proteins work together with other proteins to carry out a function, DdrC did not seem to depend on any supporting proteins to do its job. This raised the prospect that DdrC might work in other species, so the researchers tried genetically modifying E.coli bacteria to produce DdrC. They found that this increased E.coli‘s resistance to ultraviolet radiation by around 40-fold, suggesting that DdrC does indeed ‘just work’ by itself, at least in other bacteria.

The implications:

DdrC could potentially be transferred to any organism in order to improve its ability to repair damaged DNA. The most immediate application of this might be to create crops that are more resistant to extremes of ultraviolet radiation, but eventually we might see DdrC used to prevent cancer and perhaps slow down the ageing process. This will come with a host of challenges and risks to overcome, such as the immune system attacking the bacterial protein, and so we shouldn’t expect it any time soon.